Sex Differences in Glioblastoma Biology and Outcomes

Glioblastoma is the most aggressive primary brain tumour in adults, exhibiting marked disparities between male and female patients in both incidence and survival. Men are diagnosed more frequently and generally experience poorer outcomes compared with women. Underlying causes span genetic, molecular, hormonal and immunological domains. Sex-specific genetic variants modulate susceptibility, while divergent hormone receptor expression influences tumour cell proliferation and the microenvironment. Immune profiles differ by sex: male tumours often display heightened necrosis and myeloid-derived immunosuppression, coupled with greater exhaustion of cytotoxic T cells, whereas female biology confers partial protection via oestrogen-mediated pathways and more robust antitumour immunity. Metabolic factors such as tumour-derived polyamines further shape these disparities. A growing understanding of these mechanisms highlights the need for sex-stratified prognostic tools and personalised therapeutic strategies, with potential to refine immunotherapy, anti-angiogenic treatment and metabolic intervention on a global scale.

Research from Nature Portfolio

Genomic studies that stratify glioblastoma cases by sex have identified novel autosomal risk loci with differential effects. A locus at 3p21.31 shows a female-specific association, implicating genes involved in immune regulation, whereas a variant at 8q24.21 exerts a stronger influence in women than in men. These discoveries illuminate how inherited genetic architecture contributes to sex-biased tumour risk and open avenues for sex-tailored genetic screening and early detection approaches.

Sex Differences in Glioblastoma Biology and Outcomes publication trend

The graph below shows the total number of articles in sex differences in glioblastoma biology and outcomes across all publications each year (not limited to Nature Index journals).

Technical terms

Glioblastoma: The most common and aggressive primary malignant brain tumour in adults.

CD8+ T cell: A subtype of cytotoxic lymphocyte essential for antitumour immunity.

T cell exhaustion: A dysfunctional state of T cells from chronic antigen exposure, characterised by reduced proliferation and cytokine production.

Myeloid-derived suppressor cell: An immunosuppressive population of myeloid-lineage cells that dampen T cell responses.

Bevacizumab: A monoclonal antibody targeting vascular endothelial growth factor A to inhibit tumour angiogenesis.

Spermidine: A polyamine metabolite produced by tumour cells that modulates immune cell function.

References

1. Sex-biased T cell exhaustion drives differential immune responses in glioblastoma. Cancer Discovery (2023).
2. Sexual-biased necroinflammation is revealed as a predictor of bevacizumab benefit in glioblastoma. Neuro-Oncology (2024).
3. Tumor cell-derived spermidine promotes a pro-tumorigenic immune microenvironment in glioblastoma via CD8+ T cell inhibition. Journal of Clinical Investigation (2024).
4. Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21. Scientific Reports (2018).